Interaction between activated nordihydroguaiaretic acid and deoxyribonucleic acid

Abstract

Nordihydroguaiaretic acid (NDGA) is a natural product of the lignan family that has been shown to possess antimicrobial and antineoplastic properties in a variety of test systems. NDGA was observed by u.v.-visible spectroscopy to be unstable in an aqueous environment; however, by these same techniques NDGA was shown to be stable in the presence of mercaptoethanol. It is suggested that an activated NDGA is an intermediate in the O 2-mediated oxidation of NDGA and that the activated NDGA forms a stable complex when reacted with duplex DNA. This DNA-activated NDGA complex was detected and studied by both fluorescence spectroscopy and CsCl density gradient techniques. The addition of DNA quenched the fluorescence of activated NDGA in a concentration-dependent fashion. Furthermore, the exposure of activated NDGA lowered the buoyant density of DNA, also, in a concentration-dependent manner. Since mononucleotides did not quench the fluorescence of activated NDGA, and heat-denatured DNA was less effective than fully duplex DNA in its ability to interact with activated NDGA, the duplex structure of DNA was determined to be important in the complex formation. Whereas activated NDGA bound to both poly dG · poly dC and poly (dA · dT), there appeared, by one method of analysis, to be a preference for poly dG · poly dC. Activated NDGA-DNA complex was stable to dialysis, but dissociated in the presence of Sarkosyl. No changes in the viscosity or melting temperature of DNA was induced by the addition of activated NDGA. These data suggest a mechanism in which the activated NDGA was bound to the more apolar regions of duplex DNA that are located in either the major and/or minor grooves.